Gyrate atrophy of the choroid and retina is a rare inherited form of chorioretinal degeneration leading to blindness, and characterized by high plasma ornithine levels. The inborn error has been identified as a deficiency of ornithine aminotransferase (OAT). We propose studies of the biochemical lesion in this disorder, its metabolic consequences, and its therapy by nutritional and pharmacological means. We will examine the genetic heterogeneity of this disorder by enzymologic studies of cultured cells obtained from affected patients. Inherited forms of blindness in animals will be screened in an attempt to discover OAT deficiency. In addition, inhibitors of OAT will be designed and tested for their ability to induce an animal model of the disease. The metabolism of ornithine in normal retina (and in animal models) will be studied enzymologically. The effects of hyperornithinemia on the metabolism of ammonia, urea and selected amino acids will be examined in patients (and in animal models) before and after correction of hyperornithinemia and in normal subjects given ornithine loads. In patients given 13-C-labelled ornithine, turnover of ornithine and its metabolites, including polyamines, will be quantitated. The effect of impairment of de novo ornithine synthesis on flux through the urea cycle will be examined, in patients (and in animal models). Therapy for pyridoxine-unresponsive patients will entail a low arginine diet. Attempts will also be made to promote ornithinuria by designing and testing non-metabolizable inhibitors of ornithine, and to promote argininosuccinicaciduria by designing and testing irreversible inhibitors of argininosuccinic acid lyase. Long-term effects of control of plasma ornithine on ocular manifestations of the disease will be documented.